Warfarin is used by millions of Americans with conditions such as atrial fibrillation and deep venous thrombosis to lower their risk of thromboembolic events (e.g., stroke or pulmonary embolism). Although warfarin is highly efficacious when used correctly, it is also associated with high adverse event rates and lost efficacy due to poor control of anticoaguation levels. Even in specialized anticoagulation clinics that are devoted to monitoring patients on warfarin, 32% to 68% of patient time is spent out of the target therapeutic international normalized ratio (INR) range, putting patients at increased risk for thromboembolism (TE) from under-anticoagulation and bleeding from over-anticoagulation. One of the primary, modifiable contributors to poor anticoaguation control is non-adherence to warfarin. The proposed study will evaluate the effectiveness and cost-effectiveness of two novel approaches that aim to improve anticoaguation control by increasing warfarin adherence, informed by two recently completed NIH-funded studies. Both financial incentives and electronic pill reminder/feedback systems have been used successfully to modify health behaviors in a variety of health contexts. This application is for a 4-arm randomized controlled trial (RCT) in which participants receive either a lottery-based daily financial incentive;a customized, transtelephonic electronic pillbox reminder and feedback system at home;both the lottery and the electronic reminder and feedback system;or usual care (the electronic pillbox used only as a recording device with all reminders and feedback disabled). The primary specific aims will be to: 1) assess the effectiveness of a lottery-based financial incentive -- with participants eligible each day they take their medication -- on anticoagulation control relative to the control group over 6 months;2) assess the effectiveness of a customized electronic reminder and feedback system on anticoagulation control relative to the control group over 6 months;and 3) assess the joint effectiveness of the lottery-based financial incentives and electronic reminder system on anticoagulation control relative to the other groups over 6 months. Secondary aims include assessment of the cost-effectiveness of each of the above approaches, and evaluation of the impact on adherence measures and other outcomes. The proposed interventions draw on insights from behavioral economic research and are designed to be cost-effective and scalable through the use of easily applied technology. If successful, this approach could reduce the number of deaths, serious thromboembolic events, and adverse drug effects from warfarin by tens of thousands among Americans each year. PUBLIC HEALTH RELEVANCE: Warfarin is a blood thinner that, when properly used, significantly reduces the likelihood of strokes and other clotting events in millions of patients in the United States. However, many patients have difficulty taking their warfarin correctly and therefore are at high risk of strokes, other clotting events, and bleeding. In this study, we are testing the effectiveness and cost-effectiveness of two innovative approaches to improving adherence to warfarin which have the potential to reduce substantially the risk of death or significant illness for the millions of Americans for whom warfarin is a critically important medication.